Role of p38 Mitogen-Activated Protein Kinase in Asthma and COPD: Pathogenic Aspects and Potential Targeted Therapies

Drug Des Devel Ther. 2021 Mar 23:15:1275-1284. doi: 10.2147/DDDT.S300988. eCollection 2021.

Abstract

Among the various members of the mitogen-activated protein kinase (MAPK) family, p38 MAPK subgroup is the most involved in airway and lung inflammation underlying asthma and chronic obstructive pulmonary disease (COPD). In particular, several environmental agents including aeroallergens, cigarette smoke, airborne pollutants, viral and bacterial pathogens activate the p38α isoform which in turn up-regulates the expression of multiple proinflammatory cytokines and chemokines, as well as the production of some fibrogenic factors. Therefore, p38 MAPK-induced bronchial inflammation and remodelling significantly contribute to the development, persistence and amplification of airflow limitation, which is the hallmark of asthma and COPD. Such advances in our understanding of p38 role in the pathobiology of the above widespread, chronic obstructive respiratory diseases, have led to consider p38 MAPK as a suitable molecular target for novel treatment strategies. Indeed, many studies have been carried out in both animal and clinical settings, with the aim of evaluating the potential therapeutic effects of p38 MAPK inhibitors in both asthma and COPD.

Keywords: COPD; airway inflammation; asthma; p38-MAPK; p38-MAPK inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / pathology
  • Humans
  • Protein Kinase Inhibitors / pharmacology*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • p38 Mitogen-Activated Protein Kinases

Grants and funding

This paper was not funded.